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(11) | EP 2 236 151 B1 |
(12) | EUROPEAN PATENT SPECIFICATION |
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(54) |
Melanocortin receptor ligands Melanocortinrezeptorliganden Ligands des récepteurs de la melanocortine |
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Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). |
BACKGROUND OF THE INVENTION
SUMMARY OF THE INVENTION
A1 is Acc, HN-(CH2)m-C(O), L- or D-amino acid, or deleted;
A2 is Cys, D-Cys, hCys, D-hCys, Pen, D-Pen, Asp, or Glu;
A3 is Gly, Ala, β-Ala, Gaba, Aib, D-amino acid, or deleted;
A4 is His, 2-Pal, 3-Pal, 4-Pal, Taz, 2-Thi, 3-Thi, or (X1,X2,X3,X4,X5)Phe;
A5 is D-Phe, D-1-Nal, D-2-Nal, D-Trp, D-Bal, D-(X1,X2,X3,X4,X5)Phe, L-Phe or D-(Et)Tyr;
A6 is Arg, hArg, Dab, Dap, Lys, Om, or HN-CH((CH2)n-N(R4R5))-C(O);
A7 is Trp, 1-Nal, 2-Nal, Bal, Bip, D-Trp, D-1-Nal, D-2-Nal, D-Bal or D-Bip;
A8 is Gly, D-Ala, Acc, Ala, β-Ala, Gaba, Apn, Ahx, Aha, HN-(CH2)s-C(O), or deleted;
A9 is Cys, D-Cys, hCys, D-hCys, Pen, D-Pen, Dab, Dap, Om, or Lys;
A10 is Acc, HN-(CH2)t-C(O), L- or D-amino acid, or deleted;
R1 is -OH, or -NH2;
each of R2 and R3 is independently for each occurrence selected from the group consisting of H, (C1-C30)atkyl, (C1-C30)heteroalkyl, (C1-C30)acyl, (C2-C30)alkenyl, (C2-C30)alkynyl, aryl(C1-C30)alkyl, aryl(C1-C30)acyl, substituted (C1-C30)alkyl, substituted (C1-C30)heteroalkyl, substituted (C1-C30)acyl, substituted (C2-C30)alkenyl, substituted (C2-C30)alkynyl, substituted aryl(C1-C30)alkyl, and substituted aryl(C1-C30)acyl;
R4 and R5 each is, independently for each occurrence, H, (C1-C40)alkyl, (C1-C40)heteroalkyl, (C1-C40)acyl, (C2-C40)alkenyl, (C2-C40)alkynyl, aryl(C1-C40)alkyl, aryl(C1-C40)acyl, substituted (C1-C40)alkyl, substituted (C1-C40)heteroalkyl, substituted (C1-C40)acyl,
substituted (C2-C40)alkenyl, substituted (C2-C40)alkynyl, substituted aryl(C1-C40)alkyl, substituted aryl(C1-C40)acyl, (C1-C40)alkylsulfonyl, or -C(NH)-NH2;
m is, independently for each occurrence, 1, 2, 3, 4, 5, 6 or 7;
n is, independently for each occurrence, 1, 2, 3, 4 or 5;
s is, independently for each occurrence, 1, 2, 3, 4, 5, 6, or 7;
t is, independently for each occurrence, 1, 2, 3, 4, 5, 6, or 7;
X1, X2, X3, X4, and X5 each is, independently for each occurrence, H, F, Cl, Br, I, (C1-10)alkyl, substituted (C1-10)alkyl, (C2-10)alkenyl, substituted (C2-10)alkenyl, (C2-10)alkynyl, substituted (C2-10)alkynyl, aryl, substituted aryl, OH, NH2, NO2, or CN; provided that
A1 is Nle or deleted;
A2 is Cys or Asp;
A3 is Glu or D-Ala;
A4 is His;
A5 is D-Phe;
A6 is Arg;
A7 is Trp, 2-Nal or Bal;
A8 is Gly, Ala, D-Ala, β-Ala, Gaba or Apn;
A9 is Cys or Lys;
each of R2 and R3 is independently selected from the group consisting of H or (C1-C6)acyl;
provided that
(I). when R2 is (C1-C6)acyl, then R3 is H; and
(II). when A2 is Cys, then A9 is Cys,
BRIEF DESCRIPTION OF THE DRAWINGS:
Figure 1A: Mean difference in food consumed from vehicle in fasted rats 6 hours after administration of 100 nmole/Kg of selected compounds.
Figure 1B. Mean difference in food consumed from vehicle in fasted rats 6 hours after administration of 500 nmole/Kg of selected compounds.
Figure 2A. Cumulative difference in mean food intake from vehicle in rats after administration of various concentrations of Compound A.
Figure 2B. Cumulative mean body weight difference from vehicle in rats after administration of various concentrations of Compound A.
Figure 3A. Cumulative difference in mean food intake from vehicle in rats after administration of selected compounds.
Figure 3B. Cumulative mean body weight difference from vehicle in rats after administration of selected compounds.
Figure 4A. Cumulative difference in mean food intake from vehicle in rats after administration of selected compounds.
Figure 4B. Cumulative mean body weight difference from vehicle in rats after administration of selected compounds.
DETAILED DESCRIPTION OF THE INVENTION
Nomenclature and Abbreviations
Symbol | Meaning |
Abu | α-aminobutyric acid |
Ac | acyl group |
Acc | 1-amino-1-cyclo(C3-C9)alkyl carboxylic acid |
A3c | 1-amino-1-cyclopropanecarboxylic acid |
A4c | 1-amino-1-cyclobutanecarboxylic acid |
A5c | 1-amino-l-cyclopentanecarboxylic acid |
A6c | 1-amino-1-cyclohexanecarboxylic acid |
Aha | 7-aminoheptanoic acid |
Ahx | 6-aminohexanoic acid |
Aib | α-aminoisobutyric acid |
Ala or A | alanine |
β-Ala | β-alanine |
Apn | 5-aminopentanoic acid (HN-(CH2)4-C(O) |
Arg or R | arginine |
hArg | homoarginine |
Asn or N | asparagine |
Asp or D | aspartic acid |
Bal | 3-benzothienylalanine |
Bip | 4,4'-biphenylalanine, represented by the structure |
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Bpa | 4-benzoylphenylalanine |
4-Br-Phe | 4-bromo-phenylalanine |
Cha | 8-cyclohexylalanine |
hCha | homo-cyclohexylalanine |
Chg | cyclohexylglycine |
Cys or C | cysteine |
hCys | homocysteine |
Dab | 2,4-diaminobutyric acid |
Dap | 2,3-diaminopropionic acid |
Dip | β,β-diphenylalanine |
Doc | 8-amino-3,6-dioxaoctanoic acid with the structure of: |
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2-Fua | β-(2-furyl)-alanine |
Gaba | 4-aminobutyric acid |
Gln or Q | glutamine |
Glu or E | glutamic acid |
Gly or G | glycine |
His or H | histidine |
3-Hyp | trans-3-hydroxy-L-proline, i.e., (2S, 3S)-3-hydroxypyrrolidine-2-carboxylic acid |
4-Hyp | 4-hydroxyproline, i.e., (2S, 4R)-4-hydroxypyrrolidine-2-carboxylic acid |
Ile or I | isoleucine |
Leu or L | leucine |
hLeu | homoleucine |
Lys or K | lysine |
Met or M | methionine |
β-hMet | β-homomethionine |
1-Nal | β-(1-naphthyl)alanine: |
2-Nal | β-(2-naphthyl)alanine |
Nip | nipecotic acid |
Nle | norleucine |
Oic | octahydroindole-2-carboxylic acid |
Om | ornithine |
2-Pal | β-(2-pyridiyl)alanine |
3-Pal | β-(3-pyridiyl)alanine |
4-Pal | β-(4-pyridiyl)alanine |
Pen | penicillamine |
Phe or F | phenylalanine |
hPhe | homophenylalanine |
Pro or P | proline |
hPro | homoproline |
Ser or S | serine |
Tle | tert-Leucine |
Taz | β-(4-thiazolyl)alanine |
2-Thi | β-(2-thienyl)alanine |
3-Thi | β-(3-thienyl)alanine |
Thr or T | threonine |
Trp or W | tryptophan |
Tyr or Y | tyrosine |
D-(Et)Tyr | has a structure of |
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Val or V | valine |
Synthesis
EXAMPLES
Example 1: Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 SEO ID NO:7
Example 2: Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 SEQ ID NO:6
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-NH2; SEQ ID NO:1
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-A6c-Lys)-NH2; SEQ ID NO:1
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH2; SEQ ID NO:2
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ata-D-Cys)-Thr-NH2; SEQ ID NO:3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; SEQ ID NO:3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2; SEQ ID NO:3
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; SEQ ID NO:2
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2; SEQ ID NO:4
Ac-A6c-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:5
Ac-D-2-Nal-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:6
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:6
Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:7
Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:7
Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:7
Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:7
Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:8
Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:8
Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:8
Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:8
Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2;SEQ ID NO:8
Ac-Nle-c(D-Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2;SEQ ID NO:8
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEQ ID NO:9
Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEQ ID NO:9
Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEQ ID NO:9
Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQ ID NO:9
Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQ ID NO:9
Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEQ ID NO:10
Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEQ ID NO:10
Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEQ ID NO:10
Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEQ ID NO:10
Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEQ ID NO:10
Ac-Oic-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:11
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQ ID NO:11
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:11
Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:11
Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:11
Ac-hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:11
Ac-hLeu-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:11
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:11
Ac-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:11
Ac-D-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:11
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:11
n-butanoyl-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:12
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:11
Ac-β-hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:11
Ac-Gaba-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:11
Ac-Cha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; SEQ ID NO:13
Ac-hCha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; SEQ ID NO:13
Ac-Leu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; SEQ ID NO:13
Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; SEQ ID NO:13
Ac-Phe-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; SEQ ID NO:13
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-D-Ala-Lys)-NH2; SEQ ID NO:14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-β-Ala-Lys)-NH2; SEQ ID NO:14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH2; SEQ ID NO:14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH2; SEQ ID NO:14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH2; SEQ ID NO:14
Ac-Nle-c(Cys-Nis-D-Phe-Arg-D-Trp-Apn-Cys)-NH2; SEQ ID NO:15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH2; SEQ ID NO:15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NH2; SEQ ID NO:15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-NH2; SEQ ID NO:15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-NH2; SEQ ID NO:15
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; SEQ ID NO:16
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH2; SEQ ID NO:16
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-NH2; SEQ ID NO:16
n-butanoyl-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2 SEQ ID NO:17
n-butanoyl-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:17
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2; SEQ ID NO:18
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-1-Nal-Cys)-NH2; SEQ ID NO:18
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Bal-Cys)-NH2; SEQ ID NO:18
Ac-Nle-c(Cys-D-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:61
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-D-Ala-Lys)-NH2;SEQ ID NO:19
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH2; SEQ ID NO:20
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQ ID NO:21
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2;SEQ ID NO:22
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2;SEQ ID NO:22
D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr-NH2; SEQ ID NO:23
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Thr-NH2; SEQ ID NO:24
D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH2; SEQ ID NO:25
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-p-Ala-D-Cys)-Thr-NH2; SEQ ID NO:24
D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; SEQ ID NO:26
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-NH2; SEQ ID NO:26
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-NH2; SEQ ID NO:54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Ala-Cys)-NH2; SEQ ID NO:54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)-NH2; SEQ ID NO:54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEQ ID NO:54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; SEQ ID NO:54
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; SEQ ID NO:27
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH2;SEQ ID NO:28
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH2; SEQ ID NO:28
Ac-c(Cys-Glu-His-D-Phe-Arg-Trp-Ala-Cys)-NH2; SEQ ID NO:55
Ac-c(Cys-Glu-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2; SEQ ID NO:55
Ac-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2;SEQ ID NO:56
Ac-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2; SEQ ID NO:56
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2; SEQ ID NO:57
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)-NH2; SEQ ID NO:57
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEQ ID NO:57
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH; SEQ ID NO:29
Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:30
Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-NH2;SEQ ID NO:30
Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:30
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:30
Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:30
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:30
Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEQ ID NO:31
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; SEQ ID NO:32
Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; SEQ ID NO:32
Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEQ ID NO:33
Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEQ ID NO:33
Ac-Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEQ ID NO:33
Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEQ ID NO:33
Ac-Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEQ ID NO:33
Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEQ ID NO:33
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEQ ID NO:34
Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEQ ID NO:34
Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEQ ID NO:35
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; SEQ ID NO:36
Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NH2; SEQ ID NO:37
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Ala-Lys)-NH2; SEQ ID NO:58
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2; SEQ ID NO:38
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-β-Ala-Lys)-NH2; SEQ ID NO:38
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH2; SEQ ID NO:39
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH2;SEQ ID NO:39
Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:40
Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:40
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-OH; SEQ ID NO:41
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-OH; SEQ ID NO:42
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-OH; SEQ ID NO:43
D-Phe-c(Cys-His-D-Phe-Arg-Trp-p-Ala-D-Cys)-Thr-OH; SEQ ID NO:43
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-OH; SEQ ID NO:43
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-OH; SEQ ID NO:42
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-OH; SEQ ID NO:41
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO:44
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO:44
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; SEQ ID NO:29
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO:44
Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO:44
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO:44
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO:44
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO:44
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-OH; SEQ ID NO:45
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-OH; SEQ ID NO:45
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-OH; SEQ ID NO:45
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-OH; SEQ ID NO:45
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-OH; SEQ ID NO:46
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-OH; SEQ ID NO:46
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-OH; SEQ ID NO:46
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-OH; SEQ ID NO:46
Ac-Nie-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; SEQ ID NO:47
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH; SEQ ID NO:29
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:50
Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:50
Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; SEQ ID NO:51
Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; SEQ ID NO:52
Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; SEQ ID NO:52
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; SEQ ID NO:51
Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2; SEQ ID NO:53
Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2; SEQ ID NO:53
Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; SEQ ID NO:49 and
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-OH SEQ ID NO:48.
TABLES 1A and 1B - Molecular Weight and Purity for Selected Peptides
Compound | Calculated Molecular Weight | Experimental Molecular Weight | Purity | SEQ ID NO: |
1095.27 | 1095.2 | 96.4 | SEQ ID NO:1 | |
1149.36 | 1149.05 | 96 | SEQ ID NO:1 | |
1116.38 | 1115.8 | 98 | SEQ ID NO:2 | |
1167.38 | 1167.3 | 99 | SEQ ID NO:3 | |
1167.38 | 1167.5 | 93 | SEQ ID NO:3 | |
1181.41 | 1181.9 | 99 | SEQ ID NO:3 | |
1102.35 | 1103 | 99 | SEQ ID NO:2 | |
1123.32 | 1123.9 | 99 | SEQ ID NO:4 | |
1121.31 | 1121.2 | 93 | SEQ ID NO:5 | |
1193.37 | 1193.2 | 92.6 | SEQ ID NO:6 | |
1149.36 | 1149.4 | 94.5 | SEQ ID NO:6 | |
1109.3 | 1109.2 | 91.5 | SEQ ID NO:6 | |
1074.3 | 1074.6 | 98.3 | SEQ ID NO:7 | |
1074.3 | 1074.4 | 91 | SEQ ID NO:7 | |
1088.32 | 1088.4 | 93 | SEQ ID NO:7 | |
1088.32 | 1088.4 | 80 | SEQ ID NO:7 | |
1060.27 | 1060.4 | 90 | SEQ ID NO:7 | |
1074.3 | 1074.4 | 93 | SEQ ID NO:8 | |
1074.3 | 1074.4 | 81 | SEQ ID NO:8 | |
1074.3 | 1074.4 | 92 | SEQ ID NO:8 | |
1088.32 | 1088.4 | 94 | SEQ ID NO:8 | |
1088.32 | 1088.4 | 91 | SEQ ID NO:8 | |
1060.27 | 1060.4 | 96 | SEQ ID NO:8 | |
1074.3 | 1074.4 | 66 | SEQ ID NO:9 | |
1074.3 | 1074.2 | 94 | SEQ ID NO:9 | |
1088.32 | 1088.2 | 93 | SEQ ID NO:9 | |
1088.32 | 1088.4 | 90 | SEQ ID NO:9 | |
1060.27 | 1060.4 | 91 | SEQ ID NO:9 | |
1074.3 | 1074.4 | 65 | SEQ ID NO:10 | |
1074.3 | 1074.2 | 93 | SEQ ID NO:10 | |
1074.3 | 1074.4 | 92 | SEQ ID NO:10 | |
1088.32 | 1088.4 | 90 | SEQ ID NO:10 | |
1088.32 | 1088 | 95 | SEQ ID NO:10 | |
1147.35 | 1147.4 | 97.5 | SEQ ID NO:11 | |
1135.33 | 1135.1 | 99 | SEQ ID NO:11 | |
1163.39 | 1163.4 | 99 | SEQ ID NO:11 | |
1149.36 | 1149.2 | 99 | SEQ ID NO:11 | |
1107.28 | 1107 | 98.9 | SEQ ID NO:11 | |
1107.28 | 1107.4 | 99 | SEQ ID NO:11 | |
1123.32 | 1123.2 | 99 | SEQ ID NO:11 | |
1163.39 | 1163.6 | 94 | SEQ ID NO:59 | |
1143.31 | 1143.3 | 96.9 | SEQ ID NO:11 | |
1143.31 | 1143.3 | 96.5 | SEQ ID NO:11 | |
1135.33 | 1135.4 | 99 | SEQ 10 NO:11 | |
1177.41 | 1177.5 | 88.6 | SEQ ID NO:60 | |
1157.34 | 1157.2 | 70 | SEQ ID NO:11 | |
1141.36 | 1141.2 | 89 | SEQ ID NO:11 | |
1081.24 | 1080.9 | 92.5 | SEQ ID NO:11 | |
1135.33 | 1135.2 | 85 | SEQ ID NO:13 | |
1149.36 | 1149.1 | 87 | SEQ ID NO:13 | |
1095.27 | 1095.4 | 98.6 | SEQ ID NO:13 | |
1109.3 | 1109.2 | 93.8 | SEQ ID NO:13 | |
1129.29 | 1129.2 | 81.9 | SEQ ID NO:13 | |
1095.27 | 1095.3 | 97 | SEQ ID NO:14 | |
1095.27 | 1095.3 | 82 | SEQ ID NO:14 | |
1109.3 | 1109.1 | 99 | SEQ ID NO:14 | |
1137.35 | 1137.4 | 98 | SEQ ID NO:14 | |
1123.32 | 1123.3 | 97.3 | SEQ ID NO:14 | |
1102.35 | 1102 | 99 | SEQ ID NO:15 | |
1088.32 | 1087.8 | 97 | SEQ ID NO:15 | |
1116.38 | 1116.2 | 99 | SEQ ID NO:15 | |
1074.3 | 1073.8 | 99.9 | SEQ ID NO:15 | |
1074.3 | 1073.8 | 99.9 | SEQ ID NO:15 | |
1124.36 | 1123.6 | 96.1 | SEQ ID NO:16 | |
1135.38 | 1134.5 | 99.1 | SEQ ID NO:16 | |
1135.38 | 1134.6 | 94.8 | SEQ ID NO:16 | |
1113.37 | 1112.6 | 95.7 | SEQ ID NO:17 | |
1102.35 | 1101.5 | 99.9 | SEQ ID NO:17 | |
1085.32 | 1084.4 | 97.7 | SEQ ID NO:18 | |
1085.32 | 1084.5 | 96.6 | SEQ ID NO:18 | |
1091.35 | 1090.4 | 96.2 | SEQ ID NO:18 | |
1132.33 | 1131.5 | 99.9 | SEQ ID NO:61 | |
1095.27 | 1094.6 | 99.9 | SEQ ID NO:19 | |
1141.41 | 1140.5 | 95.6 | SEQ 10 NO:20 | |
1102.35 | 1101.6 | 99.9 | SEQ ID NO:21 | |
1102.35 | 1101.6 | 99.9 | SEQ ID NO:22 | |
1130.4 | 1129.6 | 99.9 | SEQ ID NO:22 | |
1181.41 | 1181.7 | 96.9 | SEQ ID NO:23 | |
1211.43 | 1211.7 | 97.1 | SEQ ID NO:24 | |
1204.44 | 1204.6 | 99 | SEQ ID NO:25 | |
1225.46 | 1225.7 | 97 | SEQ ID NO:24 | |
1218.47 | 1218.8 | 99 | SEQ ID NO:26 | |
1262.52 | 1263 | 99 | SEQ ID NO:26 | |
1131.35 | 1131.2 | 96.8 | SEQ ID NO:54 | |
1145.37 | 1145.3 | 96.4 | SEQ ID NO:54 | |
1145.37 | 1145.2 | 98.2 | SEQ ID NO:54 | |
1159.4 | 1159.2 | 95.1 | SEQ ID NO:54 | |
1173.43 | 1173.3 | 96.8 | SEQ ID NO:54 | |
1060.31 | 1060.3 | 98.5 | SEQ ID NO:27 | |
1095.27 | 1094.7 | 96.2 | SEQ ID NO:28 | |
1112.32 | 1111.7 | 96.5 | SEQ ID NO:28 | |
1090.25 | 1089.6 | 99.9 | SEQ ID NO:55 | |
1101.27 | 1100.6 | 98.3 | SEQ ID NO:55 | |
1032.22 | 1031.5 | 95.2 | SEQ ID NO:56 | |
1043.24 | 1042.5 | 95.6 | SEQ ID NO:56 | |
1144.39 | 1144.6 | 95.3 | SEQ ID NO:57 | |
1145.37 | 1144.6 | 97.3 | SEQ ID NO:57 | |
1158.41 | 1158.6 | 96.5 | SEQ ID NO:57 | |
1103.33 | 1103 | 99.9 | SEQ ID NO:29 | |
1088.32 | 1087.6 | 99.9 | SEQ ID NO:30 | |
1102.35 | 1101.7 | 99.9 | SEQ ID NO:30 | |
1116.38 | 1115.7 | 99.9 | SEQ ID NO:30 | |
1116.38 | 1115.8 | 97.4 | SEQ 10 NO:30 | |
1116.38 | 1115.5 | 96.5 | SEQ ID NO:30 | |
1156.44 | 1155.6 | 96.4 | SEQ ID NO:30 | |
1116.38 | 1115.7 | 95 | SEQ ID NO:31 | |
1116.38 | 1115.5 | 99.9 | SEQ ID NO:32 | |
1144.43 | 1144 | 99.9 | SEQ ID NO:32 | |
1088.32 | 1088 | 96.7 | SEQ ID NO:33 | |
1128.39 | 1128.4 | 95.8 | SEQ ID NO:33 | |
1088.32 | 1088.4 | 95 | SEQ ID NO:33 | |
1122.34 | 1122 | 95.2 | SEQ ID NO:33 | |
1074.3 | 1074.6 | 95.4 | SEQ ID NO:33 | |
1172.4 | 1172.2 | 95.2 | SEQ ID NO:33 | |
1046.29 | 1046.4 | 97.6 | SEQ ID NO:34 | |
1080.3 | 1080 | 95.8 | SEQ ID NO:34 | |
1099.35 | 1099.6 | 96.6 | SEQ ID NO:35 | |
1075.28 | 1075.2 | 99.9 | SEQ ID NO:36 | |
1088.32 | 1088 | 95.8 | SEQ ID NO:37 | |
1183.4 | 1182.85 | 99.9 | SEQ ID NO:58 | |
1145.33 | 1145 | 99.99 | SEQ ID NO:38 | |
1145.33 | 1145 | 99.99 | SEQ ID NO:38 | |
1138.38 | 1137.8 | 99.99 | SEQ ID NO:39 | |
1166.44 | 1166 | 99 | SEQ ID NO:39 | |
1207.4 | 1206.9 | 99 | SEQ ID NO:40 | |
1199.42 | 1198.8 | 100 | SEQ ID NO:40 | |
1117.3 | 1116.9 | 95.10 | SEQ ID NO:50 | |
1117.33 | 1116.8 | 99.2 | SEQ ID NO:50 | |
1145.38 | 1144.9 | 96.4 | SEQ ID NO:51 | |
1159.41 | 1158.9 | 99.9 | SEQ ID NO:52 | |
1159.41 | 1159.1 | 99 | SEQ ID NO:52 | |
1145.38 | 1145.1 | 99 | SEQ ID NO:51 | |
1138.3 | 1138.0 | 98.0 | SEQ 10 NO:53 | |
1138.3 | 1138.1 | 99.0 | SEQ ID NO:53 |
Compound | Calculated Molecular Weight | Experimental Molecular Weight | Purity | SEQ ID NO: |
1167.39 | 1167.40 | 99.9 | SEQ ID NO:49 |
Example 3: In vitro studies
Radioligand Binding Assays
TABLES 2A, 2B and 2C - Radioligand Binding Assay Data for Selected Compounds
Compound | Ki hMC 1-R | Ki hMC 3-R | Ki hMC4-R | Ki hMC5-R | Ki hMC1-R/ MC4-R | SEQ ID NO: |
3.87 | 10.1 | 2.09 | 430 | 1.9 | SEQ ID NO:50 | |
4.01 | 12.1 | 1.76 | 352 | 2.3 | SEQ ID NO:50 | |
8.29 | 13.3 | 2.78 | 816 | 3.0 | SEQ ID NO:51 | |
3.93 | 172 | 11.0 | 538 | 0.36 | SEQ ID NO:52 | |
1.81 | 20.5 | 4.57 | 502 | 0.4 | SEQ ID NO:52 | |
9.67 | 22.0 | 4.2 | 1900 | 2.3 | SEQ ID NO:51 | |
0.79 | 45.5 | 1.21 | 493 | 0.6 | SEQ ID NO:53 | |
0.68 | 20.7 | 1.01 | 783 | 0.7 | SEQ ID NO:53 |
Compound | Ki hMC1- R | Ki hMC 3-R | Ki hMC4-R | Ki hMC 5-R | Ki hMC1-R /MC4-R | SEQ ID NO: |
114 | 63.9 | 3.07 | 1657 | 37.1 | SEQ ID NO:16 | |
11 | 26 | 7.6 | 1800 | 1.4 | SEQ ID NO:7 | |
0.05 | 9.3 | 1.1 | 2.9 | 0.0 | SEQ ID NO:24 | |
0.07 | 4.1 | 0.85 | 8.8 | 0.1 | SEQ ID NO:27 | |
0.12 | 10 | 0.43 | 0.42 | 0.3 | SEQ ID NO:32 | |
0.05 | 1.3 | 0.47 | 0.2 | 0.1 | SEQ ID NO:34 | |
0.0996 | 9318 | 0.617 | 10.9 | 0.16 | SEQ ID NO:1 | |
.0132 | 16.1 | 1.23 | 0.359 | 0.11 | SEQ ID NO:2 | |
0.207 | 43.2 | 2.58 | 344 | 0.08 | SEQ ID NO:3 | |
0.420 | 106 | 4.75 | 1260 | 0.09 | SEQ ID NO:3 | |
0.0951 | 9.33 | 0.894 | 13.4 | 0.11 | SEQ ID NO:2 | |
0.999 | 300 | 11.1 | 431 | 0.09 | SEQ ID NO:4 | |
0.106 | 11.8 | 1.49 | 110 | 0.07 | SEQ ID NO:6 | |
0.0506 | 9.89 | 1.04 | 16.3 | 0.05 | SEQ ID NO:6 | |
0.884 | 223 | 22.5 | 609 | 0.04 | SEQ ID NO:11 | |
0.721 | 93.5 | 56.0 | 747 | 0.01 | SEQ ID NO:11 | |
0.227 | 14.5 | 2.99 | 164 | 0.08 | SEQ ID NO:11 | |
0.277 | 25.2 | 3.37 | 203 | 0.08 | SEQ ID NO:11 | |
0.323 | 14.1 | 1.96 | 24.0 | 0.16 | SEQ ID NO:15 | |
34.1 | 118 | 17.0 | 5560 | 2.01 | SEQ ID NO:21 | |
29.1 | 22.8 | 3.84 | 2550 | 7.58 | SEQ ID NO:22 | |
0.442 | 123 | 10.3 | 521 | 0.04 | SEQ ID NO:23 | |
5.80 | 3370 | 583 | 1130 | 0.01 | SEQ ID NO:25 | |
0.0567 | 31.4 | 14.7 | 9.27 | 0 | SEQ ID NO:24 | |
1.68 | 1260 | 172 | 1220 | 0.01 | SEQ ID NO:26 | |
0.128 | 85.6 | 36.9 | 38.0 | 0 | SEQ ID NO:26 | |
0.352 | 149 | 3.01 | 339 | 0.12 | SEQ ID NO:54 | |
3.93 | 876 | 48.0 | 4940 | 0.08 | SEQ ID NO:54 | |
0.995 | 287 | 4.80 | 766 | 0.21 | SEQ ID NO:54 | |
0.848 | 184 | 3.76 | 956 | 0.23 | SEQ ID NO:54 | |
1.10 | 228 | 7.58 | 859 | 0.15 | SEQ ID NO:54 | |
0.659 | 98.9 | 2.55 | 4.19 | 0.26 | SEQ ID NO:28 | |
4.12 | 445 | 50.6 | 4300 | 0.08 | SEQ ID NO:28 | |
111 | 1710 | 47.7 | 694 | 2.33 | SEQ ID NO:55 | |
262 | 2500 | 96.4 | 1460 | 2.72 | SEQ ID NO:55 | |
199 | 5990 | 96.7 | > 10000 | 2.06 | SEQ ID NO:56 | |
132 | 4560 | 40.7 | 8810 | 3.24 | SEQ ID NO:56 | |
9.12 | 1130 | 22.1 | 2860 | 0.41 | SEQ ID NO:57 | |
1.00 | 227 | 5.55 | 496 | 0.18 | SEQ ID NO:57 | |
0.536 | 169 | 3.12 | 358 | 0.17 | SEQ ID NO:57 | |
32.1 | 330 | 17.4 | 165 | 1.84 | SEQ ID NO:29 | |
10.6 | 41.1 | 7.69 | 54.9 | 1.38 | SEQ ID NO:30 | |
13.0 | 104 | 10.1 | 40 | 1.29 | SEQ ID NO:30 | |
4.28 | 38.5 | 9.0 | 12.5 | 0.48 | SEQ ID NO:30 | |
1.60 | 6.82 | 4.13 | 5.57 | 0.39 | SEQ ID NO:30 | |
12.0 | 85.8 | 11.2 | 40 | 1.07 | SEQ ID NO:30 | |
0.353 | 2.08 | 1.41 | 0.857 | 0.25 | SEQ ID NO:30 | |
0.537 | 86.1 | 5.89 | 2.56 | 0.09 | SEQ ID NO:31 | |
0.744 | 178 | 3.51 | 2.69 | 0.21 | SEQ ID NO:32 | |
0.216 | 17.4 | 0.995 | 0.486 | 0.22 | SEQ ID NO:33 | |
0.107 | 9.11 | 0.884 | 0.354 | 0.12 | SEQ ID NO:33 | |
0.148 | 13.9 | 1.06 | 0.423 | 0.14 | SEQ ID NO:33 | |
0.254 | 18.5 | 2.13 | 0.714 | 0.12 | SEQ ID NO:33 | |
0.256 | 29.9 | 1.98 | 0.864 | 0.13 | SEQ ID NO:33 | |
0.560 | 39.2 | 2.94 | 2.73 | 0.19 | SEQ ID NO:33 | |
0.186 | 15.2 | 4.93 | 0.537 | 0.04 | SEQ ID NO:34 | |
21.1 | 151 | 10.4 | 92.6 | 2.03 | SEQ ID NO:35 | |
30.7 | 152 | 15.6 | 114 | 1.97 | SEQ ID NO:36 | |
5.20 | 150 | 138 | 20.3 | 0.04 | SEQ ID NO:37 | |
4.89 | 290 | 21.3 | 11.1 | 0.23 | SEQ ID NO:58 | |
25.5 | 3.82 | 7.61 | 102 | 3.35 | SEQ ID NO:16 | |
32.5 | 5.85 | 2.53 | 94.6 | 12.85 | SEQ ID NO:16 | |
22.2 | 12.7 | 16.6 | 125 | 1.34 | SEQ ID NO:20 | |
1.17 | 1.56 | 0.277 | 3.24 | 4.22 | SEQ ID NO:38 | |
0.648 | 2.78 | 0.329 | 1.4 | 1.97 | SEQ ID NO:38 | |
0.393 | 1.86 | 0.375 | 1.11 | 1.05 | SEQ ID NO:39 | |
0.333 | 2.91 | 0.998 | 0.366 | 0.33 | SEQ ID NO:39 | |
0.461 | 2.45 | 0.931 | 1.37 | 0.50 | SEQ ID NO:40 | |
0.576 | 3.98 | 2.82 | 3.91 | 0.20 | SEQ ID NO:40 |
Compound | Ki hMC1-R | Ki hMC 3-R | Ki hMC4-R | Ki hMC 5-R | Ki hMC1-R /MC4-R | SEQ ID NO: |
17.9 | 1.68 | 0.256 | 23.4 | 69.9 | SEQ ID NO:49 |
cyclic AMP Bioassay
TABLES 3A, 3B, 3C, and 3D - cAMP Bioassay Data for Selected Compounds
Compound | EC50 hMC1-R | EC50 hMC3-R | EC50 hMC4-R | EC50 hMC5-R | EC50 hMC1-R /MC4-R | SEQ ID NO: |
5.79 | 5.25 | 0.313 | 1630 | 18.0 | SEQ ID NO:50 | |
6.17 | 5.6 | 0.397 | 1020 | 16.0 | SEQ ID NO:50 | |
26.5 | 10.5 | 0.493 | 2440 | 54.0 | SEQ ID NO:51 | |
8.43 | 32.4 | 0.959 | 2140 | 9.0 | SEQ ID NO:52 | |
4.23 | 8.09 | 0.719 | 23.2 | 6.0 | SEQ ID NO:52 | |
48.3 | 13.3 | 0.79 | 10000 | 61.0 | SEQ ID NO:51 | |
1.48 | 5.76 | 0.078 | 297 | 19.0 | SEQ ID NO:53 | |
1.39 | 2.89 | 0.055 | 467 | 25.0 | SEQ ID NO:53 |
ND = not determined |
Compound | EC50 hMC 1-R | EC50 hMC 3-R | EC50 hMC4-R | EC50 hMC5-R | EC50 hMC1-R /MC4-R | SEQ ID NO: |
2.4 | 0.33 | 0.078 | 420 | 31 | SEQ ID NO:7 | |
0.35 | 1.1 | 0.11 | 0.37 | 3 | SEQ ID NO:24 | |
0.31 | 0.27 | 0.018 | 3.1 | 17 | SEQ ID NO:27 | |
0.28 | 0.24 | 0.028 | 3.9 | 10 | SEQ ID NO:32 | |
0.37 | 0.1 | 0.021 | 1.7 | 18 | SEQ ID NO:34 | |
0.834 | 0.145 | 0.128 | 2.79 | 6.52 | SEQ ID NO:1 | |
0.76 | 0.199 | 0.0492 | 1.73 | 15.45 | SEQ ID NO:2 | |
3.26 | 0.189 | 0.0949 | 30.2 | 34.35 | SEQ ID NO:6 | |
1.37 | 0.628 | 0.131 | 3.48 | 10.46 | SEQ ID NO:6 | |
2.27 | 3.32 | 7.24 | 415 | 0.31 | SEQ ID NO:11 | |
ND | 1.89 | 0.531 | ND | ND | SEQ ID NO:21 | |
14.3 | 2.03 | 0.183 | 2240 | 78.14 | SEQ ID NO:22 | |
0.345 | 2.71 | 5376 | 2.38 | 0.06 | SEQ ID NO:24 | |
0.685 | 81.8 | 86.9 | 31.8 | 0.01 | SEQ ID NO:26 | |
0.931 | 3.22 | 1.65 | >10000 | 0.56 | SEQ ID NO:28 | |
3.24 | 0.465 | 0.0915 | 78.5 | 35.41 | SEQ ID NO:30 | |
0.819 | 0.541 | 0.453 | 45.3 | 1.81 | SEQ ID NO:30 |
ND = not determined |
Compound | EC50 hMC1-R | Kb hMC3-R | Kb MC4-R | EC50 hMC5-R | SEQ ID NO: |
17.6 | 12.4 | 38.8 | 11.8 | SEQ ID NO:16 | |
0.619 | 2.98 | 0.109 | 0.189 | SEQ ID NO:38 | |
0.913 | 0.536 | 0.346 | 0.489 | SEQ ID NO:38 | |
0.231 | 18.4 | 0.782 | 0.153 | SEQ ID NO:39 | |
0.581 | 10.8 | 0.967 | 0.126 | SEQ ID NO:39 | |
0.413 | 9.32 | 0.824 | 0.307 | SEQ ID NO:40 | |
1.27 | 3.02 | 0.442 | 0.736 | SEQ ID NO:40 | |
383 | 61.5 | 53.6 | 2842 | SEQ ID NO:16 |
Compound | EC50 hMC1-R | Kb hMC3-R | Kb MC4-R | EC50 hMC5-R | SEQ ID NO: |
193 | 5.72 | 1.58 | 1111 | SEQ ID NO:49 |
Example 4: In vivo studies
Ligand Code | Structure |
Compound A | Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 SEQ ID NO:7 |
Compound B | Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 SEQ ID NO:22 |
Compound C | Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2 SEQ ID NO:32 |
Compound D | D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Thr-NH2 SEQ ID NO:24 |
Compound E | Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 SEQ ID NO:50 |
Compound F | Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2SEQ ID NO:50 |
Compound G | Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 SEQ ID NO:51 |
Acute feeding experiments (fasting)
Acute feeding experiments (non fasting)
Chronic feeding experiments
Administration and Use
SEQUENCE LISTING
<110> BIOMEASURE, INCORPORATED
<120> MELANOCORTIN RECEPTOR LIGANDS
<130> 146P2/PCT2
<140> PCT/US2006/26586
<141> 2006-07-10
<150> US 60/748850
<151> 2005-12-09
<150> US 60/697779
<151> 2005-07-08
<160> 61
<170> PatentIn version 3.3
<210> 1
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala or 1-amino-1-cyclohexanecarboxylic acid (A6c)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 1
<210> 2
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 6-aminohexanoic acid (Ahx) or 5-aminopentanoic acid (Apn)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 2
<210> 3
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = Ala, beta-Ala or 4-aminobutyric acid (Gaba)
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDATION
<400> 3
<210> 4
<211> 8
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 5-aminopentanoic acid (Apn)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 4
<210> 5
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = 1-amino-1-cyclohexanecarboxylic acid (A6c) modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 5
<210> 6
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal), beta-cyclohexylAla (Cha) or Nle, all
modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 6
<210> 7
<211> 8
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala, beta-Ala, 4-aminobutyric acid (Gaba), alpha-aminoisobutyric acid
(Aib) or Gly
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 7
<210> 8
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = Ala, D-Ala, beta-Ala, 4-aminobutyric acid (Gaba), alpha-aminoisobutyric
acid (Aib) or Gly
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 8
<210> 9
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala, beta-Ala, 4-aminobutyric acid (Gaba), alpha-aminoisobutyric acid
(Aib) or Gly
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 9
<210> 10
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = Ala, D-Ala, beta-Ala, 4-aminobutyric acid (Gaba) or alpha-aminoisobutyric
acid (Aib)
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 10
<210> 11
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = octahydroindole-2-carboxylic acid (Oic), cyclohexylGly (Chg),
homo-cyclohexylAla (hCha), D-betacyclohexylAla (D-Cha), nipecotic acid (Nip),
homo-Pro (hPro), homo-Leu (hLeu), Phe, D-Phe, D-cyclohexylGly (D-Chg) homo-Phe (hPhe),
beta-homoMet (beta-hMet) or 4-aminobutyric acid (Gaba), all modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 11
<210> 12
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = beta-cyclohexylAla (Cha) modified with n-butanoyl
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 12
<210> 13
<211> 8
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = beta-cyclohexylAla (Cha), homo-cyclohexylAla (hCha), Leu, homo-Leu (hLeu)
or Phe, all modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Trp
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 13
<210> 14
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Trp
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = D-Ala, beta-Ala, 4-aminobutyric acid (Gaba), 7-aminoheptanoic acid (Aha)
or 5-aminopentanoic acid (Apn)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 14
<210> 15
<211> 8
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Trp
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 5-aminopentanoic acid (Apn), 4-aminobutyric acid (Gaba), 6-aminohexanoic
acid (Ahx), beta-Ala, D-Ala
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 15
<210> 16
<211> 8
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = Trp, beta-(2-naphthyl)Ala (2-Nal) or beta-(1-naphthyl)Ala (1-Nal)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 16
<210> 17
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with n-butanoyl
<220>
<221> DOMAIN
<222> (2)..(8)
<223> cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-(2-naphthyl)Ala (2-Nal) or Trp
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 17
<210> 18
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-(2-naphthyl)Ala (2-Nal), beta-(1-naphthyl)Ala (1-Nal) or 3-benzothienylAla
(Bal)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 18
<210> 19
<211> 8
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = D-Ala
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 19
<210> 20
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC-FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-beta-2-naphthylAla (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 3-benzothienylAla (Bal)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 20
<210> 21
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa = penicillamine (Pen)
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 21
<210> 22
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa = Cys or penicillamine (Pen)
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = penicillamine (Pen)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 22
<210> 23
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDATION
<400> 23
<210> 24
<211> 9
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = Arg or homo-Arg (hArg)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDATION
<400> 24
<210> 25
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = 4,4'-biphenylAla (Bip)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDATION
<400> 25
<210> 26
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe or D-(Et)Tyr
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = 4,4'-biphenylAla (Bip)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDATION
<400> 26
<210> 27
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 5-aminopentanoic acid (Apn)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 27
<210> 28
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = Trp or 3-benzothienylAla (Bal)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 28
<210> 29
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = penicillamine (Pen) or Cys
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus is the free acid
<400> 29
<210> 30
<211> 8
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-alpha-aminobutyric acid (D-Abu), D-Val, D-Ile, D-Leu, D-tert-Leu (D-Tle)
or D-beta-cyclohexylAla (D-cha)
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 30
<210> 31
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> cyclic
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa = penicillamine (Pen)
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 31
<210> 32
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa = Cys or penicillamine (Pen)
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba)
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = penicillamine (Pen)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 32
<210> 33
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Leu, beta-cyclohexylAla (Cha), Ile, Phe, Val or beta-(2-naphthyl)Ala (2-Nal),
all modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 33
<210> 34
<211> 8
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle or Phe
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 34
<210> 35
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = beta-(3-pyridiyl)Ala (3-Pal)
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 35
<210> 36
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus is the free acid
<400> 36
<210> 37
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Trp
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 37
<210> 38
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = Ala or beta-Ala
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 38
<210> 39
<211> 8
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba) or 6-aminohexanoic acid (Ahx)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 39
<210> 40
<211> 8
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = homo-Phe (hPhe) or beta-cyclohexylAla (cha), both modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 40
<210> 41
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala or 5-aminopentanoic acid (Apn)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus is the free acid
<400> 41
<210> 42
<211> 8
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 6-aminohexanoic acid (Ahx) or 5-aminopentanoic acid (Apn)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus is the free acid
<400> 42
<210> 43
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> DOMAIN
<222> (2)..(9)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = Ala, beta-Ala or 4-aminobutyric acid (Gaba)
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MOD_RES
<222> (9)..(9) is the free acid
<223> C-terminus is the free acid
<400> 43
<210> 44
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = beta-cyclohexylAla (Cha), Nle, cyclohexylGly (Chg), D-beta-cyclohexylAla
(D-cha),
homo-cyclohexylAla (hcha), D-cyclohexylGly (D-chg) or homo-Phe (hPhe), all modified
with acyl
(AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus is the free acid
<400> 44
<210> 45
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Trp
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba), 6-aminohexanoic acid (Ahx), beta-Ala or D-Ala
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus is the free acid
<400> 45
<210> 46
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = Trp, beta-(2-naphthyl)Ala (2-Nal), beta-(1-naphthyl)Ala (1-Nal) or 3-benzothienylalanine
(Bal)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus is the free acid
<400> 46
<210> 47
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa = penicillamine (Pen)
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus is the free acid
<400> 47
<210> 48
<211> 8
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba)
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = penicillamine (Pen)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus is the free acid
<400> 48
<210> 49
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MOD_RES
<222> (1)..(1)
<223> modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-beta-(2-naphthyl)Ala (D-2-Nal)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 49
<210> 50
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Arg or D-Arg, both modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 50
<210> 51
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Arg or Arg, both modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = penicillamine (Pen)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 51
<210> 52
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Arg or Arg, both modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba)
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = penicillamine (Pen)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 52
<210> 53
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Arg or Arg, both modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 53
<210> 54
<211> 9
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(9)
<223> cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = Gly, D-Ala, beta-Ala, 4-aminobutyric acid (Gaba) or 5-aminopentanoic acid
(Apn)
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDATION
<400> 54
<210> 55
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MOD_RES
<222> (1)..(1)
<223> modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = Trp or beta-(2-naphthyl)alanine (2-Nal)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 55
<210> 56
<211> 8
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MOD_RES
<222> (1)..(1)
<223> modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = Trp or beta-(2-naphthyl)Ala (2-Nal)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 56
<210> 57
<211> 9
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(9)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = Ala, beta-Ala or 4-aminobutyric acid (Gaba)
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDATION
<400> 57
<210> 58
<211> 9
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(9)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 3-benzothienylAla (Bal)
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDATION
<400> 58
<210> 59
<211> 8
<212> PRT
<213> Artificial sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-homo-cyclohexylAla (D-hcha) modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 59
<210> 60
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = beta-cyclohexylAla (Cha) modified with n-butyryl
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobutyric acid (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 60
<210> 61
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Melanocortin receptor ligand
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle modified with acyl (AC)
<220>
<221> DOMAIN
<222> (2)..(8)
<223> Cyclic
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Glu
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDATION
<400> 61
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (SEQ ID NO:50)
or a pharmaceutically acceptable salt thereof.Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (SEQ ID NR:50)
oder ein pharmazeutisch annehmbares Salz davon.Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (SEQ ID NO : 50)
ou un sel pharmaceutiquement acceptable de celui-ci.REFERENCES CITED IN THE DESCRIPTION
Patent documents cited in the description
Non-patent literature cited in the description